Inativação da síntese de óxido nítrico sintase induzível não interfere na carcinogênese esofagiana murina induzida por N-óxido de 4-nitroquinolina

Abstract

Esophageal cancer is an aggressive and frequent disease in several countries and has smoking as one of its main risk factors. Knowledge of the mechanisms behind its formation is extremely important for the development of new prevention and treatment strategies. In this sense, nitric oxide is a relevant molecule in numerous physiological conditions. There is evidence that increased expression is a relevant change in the origin of esophageal cancer. The objective of this study was to investigate the influence of the enzyme inducible nitric oxide synthase (iNOS) on esophageal carcinogenesis in an experimental model with mice with inactivation of the iNOS gene. The animals were challenged with 4NQO (carcinogen) and PPG (diluent), diluted in the water available for ingestion over 16 weeks, followed by eight weeks without exposure to the carcinogen. The occurrence of carcinomas in the epithelial lining of the esophagus was then verified in histological sections and statistically compared between the groups of wild-type (n = 23) and knockout (n = 26) animals. Finally, hematological condition was evaluated according to carcinogen exposure and occurence of epitelial displasia and carcinoma. The presence of carcinomas was identified only in animals challenged with 4NQO, demonstrating the effectiveness of the experimental model. However, in animals exposed to the carcinogen, the occurrence of carcinoma was very similar between wild-type and knockout animals. Platelet count varied according to Nos2 condition and histopathology. In short, these results do not corroborate the greater relevance of the iNOS enzyme in the occurrence of esophageal cancer, although it may have an influence on other aspects of carcinogenesis and tumor progression in this organ.